A Mechanistic Study on the Tautomerism of H-Phosphonates, H-Phosphinates and Secondary Phosphine Oxides

Abstract

H-phosphonates, H-phosphinates and secondary phosphine oxides may be preligands, and are important building blocks in the synthesis of pharmaceuticals, pesticides, and P-ligands. The prototropic tautomerism influenced by substituent effects plays an important role in the reactivity of these species. The main goal of our research was to study the tautomerism of the >P(O)H reagents by means of computational investigations applying several DFT methods at different levels. We focused on the effect of implicit solvents, and on explaining the observed trends with physical chemical molecular descriptors. In addition, multiple reaction pathways incorporating three P-molecules were elucidated for the mechanism of the interconversion.

Synthesis ofα‐Hydroxyphosphonates Containing Functionalized 1,2,3‐Triazoles

“…In this case, only the azide 5 a was effective, affording 3 a in 88 % yield (Scheme 4). These outcomes proved that diphenyl phosphite ( 2 a ) is not reactive, probably due to physical‐chemical parameters [41–42] . Despite dibenzyl phosphite 2 d has a higher reactivity and afforded the respective α ‐hydroxyphosphonate 5 b in excellent yield, this intermediate was not a suitable substrate in the reaction with phenylacetylene, and the expected product 3 m was not formed by both routes (Schemes 3, eq.2 and Scheme 4), indicating that the steric hindrance is a limitation in the CuAAC reaction.…”

“…The α ‐ and β ‐hydroxyphosphonates have demonstrated to be a versatile building block to access more elaborate structures, [32–34] and bioactive compounds, especially those containing nitrogen heterocycles (Figure 1). [35–40] The effectiveness of these reactions can be visualized by the tautomerism between the P(V) and P(III) forms, increasing their reactivity [41–42] …”

Boron Lewis Acid-Catalyzed Hydrophosphinylation of N-Heteroaryl-Substituted Alkenes with Secondary Phosphine Oxides

“…Taken together, the stronger interaction between a boron catalyst and SPO likely hampered the formation of a catalytically active species, the boron–alkene intermediate, rather than facilitating the P–H addition reaction. Finally, the reactivity trend of SPO in the hydrophosphinylation was consistent with that of the ease of tautomerization to P­(III) species, suggesting that the higher concentration of the reactive P­(III) form led to the faster conjugate addition to an alkene (Scheme c). Collectively, these observations are consistent with the proposal that the C–P bond is formed by the conjugate attack of tautomerized P­(III) to a boron–alkene species and that this C–P bond-forming step strongly influences the overall rate of the hydrophosphinylation.…”

Focusing on the Catalysts of the Pd- and Ni-Catalyzed Hirao Reactions

“…The consecutive complexation of NiCl 2 with the trivalent tautomeric form (Y 2 POH) of diphenylphosphine oxide (Y = Ph) and diethyl phosphite (Y = EtO) was evaluated by quantum chemical calculations ( Scheme 12 ). The endothermic tautomerization of Y 2 P(O)H to Y 2 POH (if Y = Ph, Δ H = 22.9 kJ mol −1 , while if Y = EtO, Δ H = 25.1 kJ mol −1 ) [ 77 ] was also taken into consideration.…”